To test the hypothesis that, in freeze-fractured membranes, the non-particulate phase is lipid, attempts are being made to intercalate lipid into cell membranes. If the density of particles, presumably protein, in a unit area decreases, then the thesis is correct. Large amounts of fatty acids (fa), injected into a carotid artery of rats, acts as a detergent and rapidly crosses vessels. Droplets of the polyunsaturated fa, linolenic acid, are osmiophilic, and can be seen fusing with the endothelial cell membrane. Droplets then cross the sarcolemma of the smooth muscle cells (SMC) of the tunica media. The fa droplets in the SMC tend to cluster around mitochrondria, whose oxidative phosphorylation is known to be uncoupled by fa. No droplets were ever seen within the nucleus of any cell type. Since the choroid plexus epithelium has numerous particles within its cell membrane, fa was also perfused thoughout the cerebral ventricles. Droplets not only entered these cells but passed extracellularly between them. Neutral lipids, such as cholesterol, are being infused for 48 hours or fed for 3 months in order to determine whether they can be intercalated more readily into stroke-prone rats as compared with normal animals. Liposomes are also being applied to cells in vivo and in vitro.